Hollow fiber having inner wall into which comb polymer is introduced, hollow fiber impregnated with gel, and fiber array thin section

ABSTRACT

This invention provides hollow fibers impregnated with gel in which the gel firmly adheres to the inner walls of the hollow fibers due to the introduction of comb polymers on the inner walls of the hollow fibers. These hollow fibers impregnated with gel have no gaps at the interfaces between the inner walls thereof and the gel. Accordingly, analysis can be performed with high accuracy. Also, thin slices obtained by bundling these hollow fibers and then slicing this bundle have sufficient adhesion between the gel and the inner walls of the hollow fibers. This also prevents gel from becoming detached from the inner walls at the time of slicing or during operations such as hybridization.

TECHNICAL FIELD

[0001] The present invention relates to hollow fibers that are used incapillary electrophoresis or the like or thin slices of a hollow fiberarray that are used as, for example, members for DNA microarrays.

BACKGROUND ART

[0002] Recently, capillary gel electrophoresis has been employed inorder to analyze trace amounts of substances in organisms. Thecapillaries employed in such a method utilize narrow tubes having innerdiameters of about 100 μm. Thus, trace amounts of samples are sufficientfor use, and samples can be easily isolated. Members that are used forthe capillaries include plastics that are excellent in theirtransparency, such as those represented by glass or polymethylmethacrylate. Use of capillaries having a hollow portion impregnatedwith a gel such as acrylamide as a member for a DNA chip that cancollectively analyze genes has been attempted (WO 00/53736).

[0003] In order to analyze organism-associated substances such as DNA bycapillary gel electrophoresis or using DNA chips, gel must be firmlyretained inside a capillary.

[0004] When the volume of gel filling the hollow portion is reduced,however, a gap is generated at the interface between the inner wall of acapillary and the gel. At the time of analysis, a substance first flowsinto the generated gap, and this disadvantageously leads to loweredaccuracy in analysis. When a capillary is used as a member for a DNAchip, the DNA chip is constructed by, for example, bundling severalcapillaries and cross-sectioning the bundle. When gel does notsufficiently adhere to the inner wall of the capillary, itdisadvantageously becomes detached from the capillary at the time ofcross-sectioning. Further, gel becomes detached from the capillaryduring analysis such as hybridization.

[0005] Introduction of a hydrophilic group on the inner wall of thecapillary has been proposed as an example of a technique for enhancingadhesion between the inner wall of the capillary and a gel (U.S. Pat.No. 5,015,350). This is, however, a technique for enhancing the adhesionbetween a gel and the capillary by coating the capillary forhydrophilization. Thus, the strength of the adhesion between a gel andthe inner wall is not sufficient, so that gel cannot be retained as thenumber of times that the capillary is used increases.

[0006] In the case of a glass capillary, a method for enhancing theability of a gel to adhere thereto by chemically modifying the innerwall thereof with polyacrylamide has been developed (S. F. Y. Li et al.,Capillary Electrophoresis, 173, 1992). This is, however, a technique forprocessing a glass surface with a bifunctional coupling agent thatreacts with a silanol group on the glass surface. Accordingly, theeffect of this technique cannot be attained by non-glass capillaries.

[0007] There has been a proposed method in which the shaping of apolymer capillary is conducted simultaneously with gel impregnation ofthe hollow portion of the capillary, thereby obtaining a polymercapillary having its hollow portion impregnated with a gel (JP PatentPublication (Kokai) No. 11-211694 A (1999)). With this technique,however, a gap is generated at the interface between the inner wall ofthe capillary and a gel when the volume of the gel is reduced during theshaping of the capillary.

[0008] Meanwhile, an attempt has been made in which hollow portions ofporous hollow fibers are filled with water-insoluble polymers for thepurpose of imparting functions such as hygroscopic properties andantistatic properties (JP Patent Publication (Kokai) No. 8-188967 A(1996)). This is, however, a technique for imparting new functions tofibers, which is unrelated to the adhesiveness of the gel filling thehollow portion.

[0009] More specifically, no conventional means had existed in the pastthat would sufficiently overcome the problem of the gap generated at theinterface between the inner wall of the capillary and the gel when thevolume of the gel is reduced or the problem of the gel becoming detachedfrom the capillary when a DNA chip is constructed. Thus, it has beendifficult to utilize a capillary impregnated with a gel for capillarygel electrophoresis or as a member for a DNA chip.

DISCLOSURE OF THE INVENTION

[0010] An object of the present invention is to provide hollow fibersthat can firmly retain gel on the inner walls of their hollow portions.It is another object of the present invention to provide hollow fibershaving their hollow portions impregnated with gel. It is a furtherobject of the present invention to provide thin slices obtained byslicing a bundle of hollow fibers having firmly immobilized gel in theirhollow portions.

[0011] The present inventors have conducted concentrated studies inorder to attain the above objects. As a result, they have found thatintroduction of comb polymers on the inner walls of hollow fibersresulted in enhanced adhesion between the inner walls of hollow fibersand the gel filling the hollow portions. This can prevent, for example,the gel from becoming detached from the inner walls of hollow fiberswhen the volume of the gel is reduced, or when the DNA chip isconstructed. This has led to the completion of the present invention.

[0012] More specifically, the present invention is as described below.

[0013] 1. Hollow fibers having comb polymers introduced on their innerwalls.

[0014] Examples of comb polymers include those having polymerizablefunctional groups or hydrophilic functional groups. An example of thebackbone of the comb polymer is polymethyl methacrylate.

[0015] 2. Hollow fibers having their hollow portions impregnated withgel.

[0016] An example of a gel is one mainly composed of an acrylamidemonomer. Such gel retains an organism-associated substance according toneed.

[0017] 3. A hollow fiber array prepared by bundling several hollowfibers impregnated with gel.

[0018] 4. Thin slices of the hollow fiber array prepared bycross-sectioning the array according to 3.

[0019] The hollow fibers used in the present invention are organicfibers. Examples thereof include: polyamide fibers such as Nylon 6,Nylon 66, and aromatic polyamide fibers; polyester fibers such aspolyethylene terephthalate, polybutylene terephthalate, polylactic acid,polyglycolic acid, and polycarbonate fibers; acrylic fibers such aspolyacrylonitrile fibers; polyolefin fibers such as polyethylene andpolypropylene fibers; polymethacrylate fibers such aspolymethylmethacrylate fibers; polyvinyl alcohol fibers; polyvinylidenechloride fibers; polyvinyl chloride fibers; polyurethane fibers;phenolic fibers; fluorine fibers comprising polyvinylidene fluoride orpolytetrafluoroethylene; and polyalkylene paraoxybenzoate fibers.

[0020] Analysis by capillary electrophoresis is conducted by radiatinglight for detection from the outer wall side of the capillary. Thus,hollow fibers are preferably optically transparent, and examples ofpreferable materials for hollow fibers are methacrylic resinsexemplified by polymethyl methacrylate (PMMA), polystyrene, orpolycarbonate that have excellent transparency.

[0021] Hollow fibers may be porous or non-porous. The outer diameters ofhollow fibers are 2 mm or smaller, and preferably 1 mm or smaller. Theinner diameters thereof are preferably 0.02 mm or larger.

[0022] In the present invention, the comb polymers that are introducedon the inner walls of the hollow fibers are composed of backbones (mainchains) and side chains (branches), and examples thereof are shown in(a) or (b) below. These comb polymers allow the gel filling the hollowportions to be firmly retained on the inner walls of hollow fibers.

[0023] (a) Comb Polymers having Polymerizable Functional Groups on theirMain or Side Chains

[0024] Examples of polymerizable functional groups include vinyl,acrylate, methacrylate, and cyclic unsaturated functional groups such ascyclohexene groups. These polymerizable functional groups are preferablyintroduced at terminuses of main or side chains of comb polymers.

[0025] Polymer components that are used as main chains of comb polymerspreferably have affinity to a material used for hollow fibers. When amaterial used for hollow fibers is polymethyl methacrylate (PMMA),monomer components that are used as main chains of comb polymers arepreferably, for example, methyl methacrylate, methyl acrylate,2-hydroxyethyl methacrylate, acrylic acid, methacrylic acid, glycidylmethacrylate, 2,3-dihydroxypropyl methacrylate, glycerol methacrylate,2-hydroxyethyl acrylate, or 2-hydroxypropyl acrylate. Two or more kindsof these monomers can be copolymerized.

[0026] (b) Comb Polymers having Affinity to a Gel Filling the HollowPortions

[0027] As with the case of (a) above, polymer components that arehydrophilic with materials used for hollow fibers should be selected aspolymer components for main chains. Preferably, polymer components ofside chains have affinity sufficiently to the network structure of thegel filling the hollow portion of the hollow fibers and are capable ofbecoming entangled with the network structure of a polymeric gel.

[0028] For example, if the gel filling the hollow portion ishydrophilic, a side chain polymer preferably has a hydrophilicfunctional group. Examples of a hydrophilic functional group include apolymer comprising hydroxyethyl methacrylate, ethylene glycol, propyleneglycol, vinyl alcohol, acrylic acid, or acrylamide as a constitutionalunit or a copolymer of two or more thereof. In addition thereto, apolymer comprising a hydrophilic functional group such as a hydroxyl,amino, or sulfonic acid group introduced at its terminus can be selectedas a side chain.

[0029] The molecular weight of the polymer that is introduced on theside chain is preferably between 20 and 300,000, and more preferablybetween 1,000 and 10,000.

[0030] Comb polymers can be introduced on the inner wall of the hollowfiber by immersing one end of the hollow fiber in a solution of combpolymers and suctioning the solution from the other end. In such a case,the solution of comb polymers introduced by suction is preferablydischarged in order to avoid blockage in the hollow portion orembrittlement of hollow fibers caused by dissolution of inner walls ofhollow fibers. After the polymer solution is discharged, a solvent thatdissolves the comb polymers is allowed to evaporate by air-drying, andthe comb polymers are then allowed to adhere to the inner walls ofhollow fibers.

[0031] The concentration of the comb polymers are preferably 50% by massor lower, and more preferably 1% to 10% by mass.

[0032] In order to allow the comb polymers described in (a) and (b)above to uniformly adhere to the inner walls of hollow fibers, a solventthat dissolves the comb polymers is preferably a good solvent for thecomb polymers and a poor solvent for materials used for hollow fibers.Examples of preferable solvents include alcohols such as methanol,ethanol, and propanol, acetone, methyl ethyl ketone, acetonitrile,dioxane, dimethylformamide, dimethylacetamide, dimethylsulfoxide,toluene, and ethyl acetate. These solvents can be used solely or incombinations of two or more. When several solvents are used incombination, the solvents to be combined are preferably miscible witheach other, and solvents to be mixed are preferably solely good solventsfor the comb polymers.

[0033] In the present invention, the kinds of gel used to fill thehollow portions are not particularly limited. Examples of a gel that canbe used include a gel prepared by allowing a cross-linked polymer toswell with the aid of water, wherein the cross-linked polymer isprepared by copolymerizing at least one monomer selected from amongacrylamide, N,N-dimethylacrylamide, N-isopropylacrylamide,N-acryloylaminoethoxyethanol, N-acryloylaminopropanol,N-methylolacrylamide, N-vinylpyrrolidone, hydroxyethyl methacrylate,(meth)acrylic acid, allyl dextran, and the like with a polyfunctionalmonomer such as methylene bis(meth)acrylamide, or polyethylene glycoldi(meth)acrylate.

[0034] Examples of polymerization initiators that can be used includeazo, peroxide, or redox initiators that can be dissolved in the solventto be used. Examples thereof include 2,2′-azobisisobutyronitrile,2,2′-azobis(2-methyl butyronitrile)isobutyronitrile, benzoyl peroxide,and benzoyl peroxide/dimethylaniline.

[0035] Examples of other gels include gels such as agarose, alginicacid, dextran, polyvinyl alcohol, or polyethylene glycol and gelsprepared by cross-linking these gels.

[0036] When the hollow fibers of the present invention are used fornucleic acid analysis, the gel used to fill the hollow portion ispreferably an acrylamide gel. The concentration level of an acrylamidemonomer is preferably 2% to 20% by mass.

[0037] A gel is commonly used to fill the hollow portion of the hollowfiber through suction in vacuo, although the technique used therefor isnot limited thereto.

[0038] When the comb polymer as described in (a) above is used, apolymerizable functional group thereof is chemically bound to a gelcomponent, thereby allowing the gel used to fill the hollow fibers to befirmly retained on the inner walls of the hollow fibers. Morespecifically, a monomer component, which is a starting material for agel component, fills the hollow fiber comprising the comb polymerdescribed in (a) introduced on its inner wall, and a polymerizablefunctional group of the comb polymer described in (a) is allowed toreact with the monomer component when polymerizing monomer components.

[0039] When the comb polymer described in (b) above is used, a gelfilling the hollow fiber can be firmly retained on its inner wall uponthe entanglement of the network structure of the gel filling the hollowfiber and the side chain of the comb polymer (b).

[0040] In the present invention, examples of organism-associatedsubstances include those selected from the group consisting of thefollowing substances 1 to 3:

[0041] 1. a nucleic acid, amino acid, sugar, or lipid;

[0042] 2. a polymer comprising at least one of substance 1. above; and

[0043] 3. a substance interacting with substance 1 or 2.

[0044] When a nucleic acid is used as an organism-associated substance,for example, DNA can be prepared from a living cell by the method ofBlin et al. (Nucleic Acids Res. 3. 2303, 1976), and RNA can be extractedtherefrom by the method of Favaloro et al. (Methods. Enzymol. 65, 718,1980). Also, chain or cyclic plasmid DNA or chromosome DNA can be used.A DNA fragment that has been cleaved with a restriction enzyme orchemically, DNA that has been synthesized with the aid of an enzyme orthe like in vitro, or DNA that has been synthesized chemically can beused as such DNA.

[0045] Organism-associated substances can be retained by the gel byphysically embedding them in the gel or directly binding them to gelconstituents. Alternatively, organism-associated substances may be firstallowed to bind to carriers such as polymers or inorganic particles bycovalent or non-covalent bonds, thereby immobilizing the carriers in thegel.

[0046] An embodiment of a direct bond to a gel constituent is carriedout by introducing a vinyl group to a nucleic acid terminus and thenallowing the resultant to copolymerize with a gel constituent, such asacrylamide (WO 98/39351). Also, agarose is converted to imide carbonateby the cyanogen bromide method, and the resultant is bound to an aminogroup of a nucleic acid having an aminated terminus, thereby gelatingthe agarose. Alternatively, a biotinized nucleic acid can be allowed toreact with avidinized agarose beads (for example, avidinized agarose,manufactured by Sigma), thereby obtaining agarose beads having nucleicacids immobilized thereon. The agarose beads having nucleic acidsimmobilized thereon can be immobilized in acrylamide gel or the like.

[0047] Several hollow fibers comprising the thus prepared gel comprisingan organism-associated substance retained thereby filling their hollowportions are bundled, and the bundle of fibers is cross-sectioned. Thus,thin slices of the hollow fiber array can be prepared.

[0048] Examples of methods for bundling several hollow fibers include:(a) a method in which several hollow fibers are arranged in parallel andimmobilized on a sheet such as an adhesive sheet, and the sheet is woundin a spiral configuration, thereby forming a bundle; and (b) a method inwhich two porous plates with several openings are stacked, a hollowfiber is allowed to pass through each opening of these porous plates,and the interval between two porous plates is widened, thereby forming abundle.

[0049] In the method as described in (b) above, a tension should beimparted to each fiber in order to maintain the regularity of thesequence after the fibers have been allowed to pass through the porousplates. Accordingly, fibers are preferably highly elastic, and examplesthereof include materials comprising methacrylic resins such as aromaticpolyamide or methyl methacrylate.

[0050] A bundle of hollow fibers is immobilized by causing resins or thelike to flow into the gap between two fibers. The immobilized bundle offibers is cross-sectioned using a microtome or the like. Thus, thinslices can be obtained. The thin slices preferably have thicknesses of 1mm or smaller.

[0051] The thin slices are employed for the collective analysis ofseveral genes. Thus, the number of hollow fibers in one thin slice ispreferably large. Preferably, 100 or more fibers are present per cm²thereon. The outer diameters of the hollow fibers used are preferablysmall. They are preferably 0.5 mm or smaller, and further preferably 0.3mm or smaller. The inner diameters are preferably 0.02 mm or larger.

[0052] Organism-associated substances that are retained in hollow fibersin thin slices may differ depending on the type of hollow fiber.Alternatively, a group of several hollow fibers comprising the sameorganism-associated substances being retained therein may be placed inthin slices.

[0053] The thus prepared thin slices of hollow fiber arrays retainingorganism-associated substances are used as, for example, a tool forcollective analysis of genes.

[0054] This description includes part or all of the contents asdisclosed in the description of Japanese Patent Application No.2001-232751, which is a priority document of the present application.

BRIEF DESCRIPTION OF THE DRAWING

[0055]FIG. 1 schematically shows an apparatus for introducing a solutionof comb polymers on the inner walls of hollow fibers, wherein referencenumeral 11 indicates a bundle of fibers, reference numeral 12 indicatesa vessel filled with a solution of comb polymers, reference numeral 13indicates a trap tube, and reference numeral 14 indicates a vacuum pump.

BEST MODES FOR CARRYING OUT THE INVENTION

[0056] The present invention is described in greater detail withreference to the following examples.

EXAMPLE 1

[0057] (1) Production of Comb Polymers having Polymerizable FunctionalGroups on their Side Chains

[0058] Methyl methacrylate (MMA, 100 parts), glycidyl methacrylate (GMA,100 parts), and azobisisobutyronitrile (AIBN, 0.5 parts) were addeddropwise to methyl ethyl ketone (MEK, 50 parts) at 80° C. in thenitrogen gas stream (50 cc/min) for 3 hours.

[0059] Thereafter, AIBN (0.1 parts) and MEK (70 parts) were added, theresultant was allowed to stand for 1 hour, AIBN (0.1 parts) and MEK (10parts) were added, the resultant was allowed to stand for 3 hours, andMEK (50 parts) was further added. Thereafter, methylhydroquinone (MEHQ,0.5 parts), triphenylphosphine (2.5 parts), and acrylic acid (99 mole %of GMA) were added. During these procedures, reaction was allowed toproceed for 30 hours while air was blown thereinto (100 cc/min), andcomb polymers (A) having vinyl groups added to their side chainterminuses were obtained. These copolymers had 25 mole % of vinyl groupsintroduced therein.

[0060] (2) Production of Hollow Fibers Comprising Comb PolymersIntroduced Therein

[0061] 50 hollow fibers of polymethyl methacrylate (outer diameter: 300μm, inner diameter: 200 μm, length: 60 cm, manufactured by MitsubishiRayon Co., Ltd.) were bundled, and comb polymers (A) were introduced intheir hollow portions using the apparatus shown in FIG. 1. In FIG. 1,one end of fiber bundle 11 was connected to trap tube 13. Another endwas placed in vessel 12 filled with polymer solution 1. Vacuum pump 14was activated to introduce the polymer solution 1 in the hollow portionsby suction.

[0062] A part of the solution introduced by suction into the hollowportions was transferred to the trap tube, and the solvent remaining onthe inner walls of the hollow portions was allowed evaporate by airdrying. Thus, hollow fibers, the comb polymers (A) having beenintroduced on the inner walls of their hollow portions, were obtained.[Polymer solution 1] Comb polymer (A)  5% by mass 1,4-dioxane 95% bymass

[0063] (3) Production of a Hollow Fiber Array

[0064] Two porous plates (thickness: 0.1 mm) each comprising 49 pores intotal arranged in 7 rows in both lengthwise and breadthwise directions,having pore diameters of 0.32 mm, and having the center-to-centerdistances between neighboring pores of 0.42 mm were stacked. 49 hollowfibers of polymethyl methacrylate prepared in (2) above were allowed topass through each pore of these two porous plates. The interval betweenthe two porous plates was 50 mm, and both ends were immobilized whilethreads were being stretched therebetween.

[0065] Subsequently, a starting material for resin was made to flow intothe vicinity of the hollow fiber array and then allowed to harden.Polyurethane resin adhesives (Nippolan 4276, Coronate 4403, manufacturedby Nihon Polyurethane Industry Co., Ltd.) were used. After the resin hadhardened, the porous plates were removed. Thus, a resin block containinghollow fibers was obtained.

[0066] (4) Production of Oligonucleotide having a Methacrylate Group

[0067] An oligonucleotide was synthesized using an automatic DNA/RNAsynthesizer (model 1394, manufactured by Applied BioSystems (formerly PEBiosystems)). In the final step of synthesis, the reaction was allowedto proceed using Aminolink II (manufactured by Applied BioSystems) tosynthesize an oligonucleotide having aminated terminuses.

[0068] The resulting GCAT with aminated terminuses (50 μl, 500 nmol/ml),glycidyl methacrylate (5 μl), and dimethylformamide (DMF, 5 μl) weremixed, the mixture was allowed to react at 70° C. for 2 hours, and 190μl of water was added thereto. Thus, GCAT having 100 nmol/ml ofmethacrylate groups (MA-GCAT) was obtained.

[0069] (5) Impregnation of Hollow Portions with Gel

[0070] Subsequently, a starting solution for a gel comprising themonomer and the initiator with the following mass ratios was prepared.Acrylamide   9 parts by mass N,N-methylenebisacrylamide   1 part by mass2,2′-azobis(2-methylpropionamidine) 0.1 part by mass dihydrochioride(V-50) Water  90 parts by mass

[0071] MA-GCAT prepared in (4) was added to the above solution in such amanner that the solution would comprise MA-GCAT at 0.5 nmol/l.

[0072] The hollow portions of hollow fibers in the resin block obtainedin (3) were filled with this mixed solution, the block was transferredinto a hermetically sealed glass vessel with its inside being saturatedwith moisture, and the content of the vessel was allowed to stand at 70°C. for 3 hours for polymerization. Thus, a gel was generated, and ablock of a hollow fiber array having its hollow portion impregnated withgel was obtained.

[0073] (6) Production of Thin Slices of a Hollow Fiber Array

[0074] This block of hollow fiber array was sliced to a thickness of 500μm in a direction vertical to the direction of fibers to obtain thinslices. Gel did not become detached from the inner walls at the time ofslicing. Thus, it was confirmed that the adhesion at the interfacebetween the inner walls of the hollow fibers and the gel wassufficiently strong. The conditions of the gel in the hollow portionswere observed using a stereoscopic microscope. As a result, all the 49hollow fibers were impregnated with acrylamide gel without any spaces.

EXAMPLE 2

[0075] Thin slices of a hollow fiber array were prepared in the samemanner as in Example 1, except that polymer solution 2 was used insteadof polymer solution 1. [Polymer solution 2] PMMA monoacrylate  5 partsby mass (molecular weight: 6,000) Toluene 95 parts by mass

[0076] Gel did not become detached from the inner walls at the time ofslicing. Thus, it was confirmed that the adhesion at the interfacebetween the inner walls of the hollow fibers and the gel wassufficiently strong. The conditions of the gel in the hollow portionswere observed using a stereoscopic microscope. As a result, all the 49hollow fibers were impregnated with acrylamide gel without any spaces.

EXAMPLE 3

[0077] Thin slices of a hollow fiber array were prepared in the samemanner as in Example 1, except that hollow fibers of polycarbonate(outer diameter: 250 μm, inner diameter: 130 μm, length: 60 cm,Mitsubishi Rayon Co., Ltd.) were used instead of hollow fibers ofpolymethyl methacrylate, and polymer solution 3 was used instead ofpolymer solution 1. [Polymer solution 3] Comb polymer (A)  5 parts bymass 1,4-dioxane/acetonitrile (12%/88%) 95 parts by mass

[0078] Gel did not become detached from the inner walls at the time ofslicing. Thus, it was confirmed that the adhesion at the interfacebetween the inner walls of the hollow fibers and the gel wassufficiently strong. The conditions of the gel in the hollow portionswere observed using a stereoscopic microscope. As a result, all the 49hollow fibers were impregnated with acrylamide gel without any spaces.

EXAMPLE 4

[0079] (1) Production of Comb Polymers having Affinity to a Gel FillingHollow Portions-1

[0080] The comb polymer (A) obtained in Example 1 (1 part) and2,2′-azobis(2-methylpropionamidine) dihydrochloride (V-50, 0.1 parts) asan initiator were placed in a polymerization tube, they were dissolvedin 100 parts of hydroxyethyl methacrylate (HEMA), the inside of the tubewas deaerated, and the tube was then sealed to conduct polymerization at60° C. After the completion of the polymerization, the sealed tube wasopened and the content thereof was poured into ethanol. Thus, aprecipitate of the comb polymer (B) having polyHEMA added to its sidechain was obtained. A homopolymer of HEMA as a by-product wassupplemented in an ethanol phase.

[0081] (2) From Introduction of Comb Polymers to Production of ThinSlices of Hollow Fiber Array

[0082] Thin slices of a hollow fiber array were prepared in the samemanner as in Example 1, except that polymer solution 4 was used insteadof polymer solution 1. [Polymer solution 4] Comb polymer (B)  5 parts bymass 1,4-dioxane 95 parts by mass

[0083] Gel did not become detached from the inner walls at the time ofslicing. Thus, it was confirmed that the adhesion at the interfacebetween the inner walls of the hollow fibers and the gel wassufficiently strong. The conditions of the gel in the hollow portionswere observed using a stereoscopic microscope. As a result, all the 49hollow fibers were impregnated with acrylamide gel without any spaces.

EXAMPLE 5

[0084] Thin slices of a hollow fiber array were prepared in the samemanner as in Example 3, except that polymer solution 5 was used insteadof polymer solution 3. [Polymer solution 5] Comb polymer (B)  5 parts bymass 1,4-dioxane/acetonitrile (12%/88%) 95 parts by mass

[0085] Gel did not become detached from the inner walls at the time ofslicing. Thus, it was confirmed that the adhesion at the interfacebetween the inner walls of the hollow fibers and the gel wassufficiently strong. The conditions of the gel in the hollow portionswere observed using a stereoscopic microscope. As a result, all the 49hollow fibers were impregnated with acrylamide gel without any spaces.

EXAMPLE 6

[0086] (1) Production of Comb Polymers having Affinity to a Gel FillingHollow Portions-2

[0087] The comb polymer (A) obtained in Example 1 (1 part) and V-50 (0.1parts) as an initiator were placed in a polymerization tube, they weredissolved in 100 parts of polyethylene glycol monoacrylate (manufacturedby Aldrich), and the tube was then sealed to conduct polymerization at60° C. After the completion of the polymerization, the solution waspoured into water. Thus, the comb polymer (C) having polyethylene glycoladded to its side chain was obtained. A homopolymer of polyethyleneglycol monoacrylate as a by-product was separated in an aqueous phase.

[0088] (2) From Introduction of Comb Polymers to Production of ThinSlices of Hollow Fiber Array

[0089] Thin slices of a hollow fiber array were prepared in the samemanner as in Example 1, except that polymer solution 6 was used insteadof polymer solution 1. [Polymer solution 6] Comb polymer (C)  5 parts bymass 1,4-dioxane 95 parts by mass

[0090] Gel did not become detached from the inner walls at the time ofslicing. Thus, it was confirmed that the adhesion at the interfacebetween the inner walls of the hollow fibers and the gel wassufficiently strong. The conditions of the gel in the hollow portionswere observed using a stereoscopic microscope. As a result, all the 49hollow fibers were impregnated with acrylamide gel without any spaces.

EXAMPLE 7

[0091] (1) Production of Comb Polymers having Affinity to a Gel FillingHollow Portions-3

[0092] The comb polymer (A) obtained in Example 1 (1 part) andacrylamide (100 parts) were dissolved in 100 parts of ethanol, and aninitiator solution (an aqueous solution of 10% ammonium persulfate, 0.1parts) was added thereto to conduct polymerization at 60° C. After thecompletion of the polymerization, the solution was poured into water.Thus, the comb polymer (D) having polyacrylamide added to its side chainwas obtained. Polyacrylamide as a by-product was separated in an aqueousphase.

[0093] (2) From Introduction of Comb Polymers to Production of ThinSlices of Hollow Fiber Array

[0094] Thin slices of a hollow fiber array were prepared in the samemanner as in Example 1, except that polymer solution 7 was used insteadof polymer solution 1. [Polymer solution 7] Comb polymer (D)  5 parts bymass 1,4-dioxane 95 parts by mass

[0095] Gel did not become detached from the inner walls at the time ofslicing. Thus, it was confirmed that the adhesion at the interfacebetween the inner walls of the hollow fibers and the gel wassufficiently strong. The conditions of the gel in the hollow portionswere observed using a stereoscopic microscope. As a result, all the 49hollow fibers were impregnated with acrylamide gel without any spaces.

COMPARATIVE EXAMPLE 1

[0096] Thin slices of a hollow fiber array were prepared in the samemanner as in Example 1, except that polymer solution 8 was used insteadof polymer solution 1. [Polymer solution 8] Copolymer of methylmethacrylate  5 parts by mass and methacrylic acid (Coating Resin PB2322, manufactured by Mitsubishi Rayon Co., Ltd.) Ethanol 95 parts bymass

[0097] The conditions of the gel in the hollow portion were observed. Asa result, it was found that none of the gel had become detached from thehollow portion, although a gap was observed at the interface between theinner wall of the hollow fiber and the gel.

[0098] All publications, patents, and patent applications cited hereinare incorporated herein by reference in their entirety.

[0099] Industrial Applicability

[0100] Use of hollow fibers having comb polymers introduced on theirinner walls can provide hollow fibers impregnated with gel in which thegel is firmly retained on the inner walls of hollow fibers. Thin slicesobtained by bundling these hollow fibers and slicing the bundle havesufficient adhesion between the gel and the inner walls of hollowfibers.

1. Hollow fibers having comb polymers introduced on their inner walls.2. The hollow fibers according to claim 1, wherein the comb polymershave polymerizable functional groups.
 3. The hollow fibers according toclaim 2, wherein the polymerizable functional groups are vinyl groups.4. The hollow fibers according to claim 1, wherein the comb polymershave hydrophilic functional groups.
 5. The hollow fibers according toclaim 1, wherein the backbones of the comb polymers are polymethylmethacrylate.
 6. Hollow fibers impregnated with gel, wherein the hollowportions of the hollow fibers according to claim 1 are filled with gel.7. The hollow fibers impregnated with gel according to claim 6, whereinthe gel is mainly composed of an acrylamide monomer.
 8. Hollow fibersimpregnated with gel, wherein organism-associated substances areretained in the gel in the hollow fibers impregnated with gel accordingto claim
 6. 9. A hollow fiber array, wherein several of the hollowfibers impregnated with gel according to claim 6 are bundled.
 10. Thehollow fiber array according to claim 9, which comprises 100 or morefibers per cm² thereon.
 11. Thin slices of the hollow fiber array, whichare prepared by cross-sectioning the hollow fiber array according toclaim 9.